Bis-(halophenyl)-fluoroaliphatic compounds as ddt synergists



United States Patent 2,990,321 BIS-(HALOPHENYL)-FLUOROALIPHATIC COM- POUNDS AS DDT SYNERGISTS Joseph Bernstein, Brighton, Mass., Murray S. Blum, Baton Rouge, La., and John J. Pratt, Jr., Wayland, ass., assignors to the United States of America as represented by the Secretary of the Army No Drawing. Filed July 28, 1958, Ser. No. 751,579 21 Claims. (Cl. 167-30) (Granted under Title 35, US. Code (1952), sec. 266) FCF Hal Hal wherein Hal and Hal are halogen atoms of an atomic weight not above 80 (i.e., fluorine, chlorine and bromine), and wherein Y is hydrogen, hydroxyl or acetoxyl. Compounds falling under this general formula are 2,2-difluoro 1,1-bis-(p-halophenyl)-ethanes, 2,2-difiuoro-1,1 bis (p halophenyl) -ethanols, and 2,2-difiuoro-1, l-bis- (p-halophenyl) -ethyl acetates. Also'within the purview of our invention are dehydrofiuoro ethene analogs of 2,2-difiuoro-1,l-bis- (p-halophenyl)-ethanes, which analogs have the general formula: n

REF

7 Hal al' The foregoing compounds'may be prepared -'by -a Grignard type reaction, as will be more fully explained hereafter. v

Tests have shown that among the foregoing coinpounds the 2,2-difluoro-1,l-bis-(p-halophenyD-ethanols are highly potent insecticides, and are surprisingly and strikingly effective as synergists for DDT; these effects are particularly striking when the halogen atoms on the respective phenyl groups are either chlorine or bromine. However, the other compounds herein disclosed are likewise valuable weapons in the arsenal of economic entomology, inasmuch as experience has shown that succeeding generations of insects quickly acquire immunity to a given type of insecticide through the breeding of resistant strains. It is therefore important to have alternate insecticides and insecticidal synergists on hand to combat insects which have thus acquired immunity'against a previously very effective insecticide.

We are now aware (though this was not known to us at the outset of our research) that 2,2,2-trifluoro-l,1-bis- (p-halophenyl)-ethanes, ethanols and ethyl acetates have been disclosed as synergistsfor DDT (see Tahori in Journal of Economic Entomology, 1955, vol. 48, pp. 638- 642, and Kaluszyner et al. in American Chemical Society Journal, 1955, vol. 77, pp. 4164-4168); however, we have found surprisingly that our 2,2-di-fluoro compounds have unexpectedly more powerful synergistic insecticidal 'action in combination with DDT than the results obtained by the foregoing workers with 2,2,2-trifluoro compounds would have permitted to expect.

We will now proceed to illustrate the practice of our invention by means of several examples, but wish to have it understood that we do not intend to limit the practice of our invention to the particular methods therein set forth, inasmuch as our novel compounds can be made by other syntheses and may be combined with DDT in any desired'proportion, as may be most effective under the circumstances of a particular application.

Freshly purified ethyl difluoroacetate (20.0 g., 0.16 mole), diluted with an equal volume of ether, was added with stirring in the course of 1, hr. to the ice-cold Grig nard reagent prepared from 10.7 g. (0.44 g.-atom) of magnesium turnings-and 81 g. (0.44 mole) of 1-bromo-4= chlorobenzene in ml. of ether. Stirring and cooling in the ice-bath were maintained for 2 hours after completion of the addition of the ester. The reaction mixture, after standing at room temperature overnight, was treated, While stirring and cooling, with saturated ammonium chloride, prepared by shaking 40 g. of the salt with 100 ml. of water. The yellow suspension was filtered with suction through a sintered-glass funnel, the filter cake was washed with ether, and the combined ethereal extract washed twice with water before being dried over sodium sulfate. Evaporation of the ether yielded a dark orange oil which was diluted with an equal volume of methanol and refrigerated at 35 for 2 days in order to'allow the traces of biphenyl' to crystallize. Filtration of the mixture followed by steam distillation of the filtrate (21: of distillate was collected and discarded) gave a product which was essentially free of starting material and derived products. The oily residue was dissolved in ether'and dried oversodiumsulfate. Removal of the solvent and distillation of the residue af fordeda 53% yield of 2,2-difluoro-1,1-bis-(p-chloro{ 'phenyl')-,ethanol, a liquid having a B.P. of 136 C..at 0.20 mm.; index of refraction in, 1.5780. With concentrated H 80 it gave a cherry-red color. Analysis (cis iji a a i 0 Calculated Found The m-chlorophenyl and o-chlorophenyl analogs are produced by substituting the same amounts of l-bromo-' 3-chlorobenzene or 1-bromo-2-chlorobenzene in lieu of the 1-bromo-4-chlorobenzene of the above example.

EXAMPLE 2 2,2-diflu0r0-1,1-bis-(p-brom0phenyl)-ethanol Example 1 was repeated, but a stoichiometrically equivalent amount (104 grams; 0.44 mole) of 1,4-dibromobenzene was used in lieu of 1-bromo-4-chlorobenzene. A 40% yield of 2,2-difluoro-1,l-bis-(p-bromophenyl)- ethanol was obtained as a liquid which had a boiling point of 153-164 C. at 0.17 mm; index of refraction 'n 1.6039. With concentrated H 50 it gave a red color. Analysis (C H Br F O):

' Calculated Found 3 f Upon prolonged standing, thick prisms formed, having a M.P. of 545-56 C.

EXAMPLE 3 aesdsar i Example 1 was repeated, but a stoichiometrically equivalent amount (0.44 mole) of l-bromo-4fluorobenzene was used in lieu of l-bromol -ehlorobenzene. A 43% yield of 2,2-difiuoro-l,l-bis-(p-fiuorophenyl)-ethanol was obtained in liquid form having a B.P. of 99-100 C. at 0.05 mm.; index of refraction r2 1.5276. With concentrated H 50 it gave a red-orange color. Analysis 14 1u 4 after being washed with waterr Removal of the ether and distillation of the residue in vacuo yielded an oil which spontaneously crystallized. The crude crystals were recrystallized by means of a methanol-water solvent, and a 90% yield of 2.,2-difluoro-l,l-bis-(p-chlorophenyl)- ethane crystals having a M.P. of 37.5 -38.5 C. and a B.P. of 110-118 C. at 0.08 mm; pressure was obtained; Analysis (C14HmC13F )Z Calculated Found Calculated Found C 62. 23 62. 5 H 3. 73 p 3. 7

EXAMPLE 4 2,2-diflu0ro-l,1-bis-(p-hal0phenyl)-ethyl acetate Calculated Found I 2,2 F difluoro 1,1 bis (p bromophenyllethyl acetate crystals having a M.P. of 80-805 C. were obtained in the same manner in an 86% yield from the 2,2'-difluoro-1,1-bis (p-br0mophenyl)eethanol of Example 2). (C16H12BI'2F202): I 4 I l A Calculated Found 7 44.25 44.3 2.79 2.9 H 36.8 ae.s

' An 89% yield of 2,2-difluoro-1,1-bis-(p-fluorophenyl) ethyl acetate was obtained in liquid form from the 2,2 difluoro-1,1-his-(p-fiuorophenyl)-ethanol of Example 3; it resisted attempts to induce crystallization and isolated as a very viscous oil at 80 C. and 0.1 mm. pressure;

index of refraction 11 1.5158. Analysis (C18H12FO2):

EXAMPLE 5 2,2-diflu0ro-1,1-bis-(p-halophenyl) -ethane 8.0-10.0 grams of 2,2 difiuoro 1,1 bis (p chloro phenyD-ethanol (Ex. 1) were heated under reflux for ten days with a mixture'of 3.5 g. of red phosphorus, 1.27 a

g. of iodine, 50 ml. of glacial acetic acid, and 1.0 ml. of water. The cooled reaction mixture was filtered with suction directly into a separatory funnnel containing 300' ml. of 2.5% sodium bisulfite. The oily suspension was neutralizedby adding portions of solid sodium bicarbona ate with intermittent shaking and was then extracted with ether. The ether extract was dried over sodium sulfate 2,2-difluoro-1,1-bis-(p brom'ophenyl) ethane crystals were obtained in a 89% yield from the 2,2-difluoro-l,1- bis-(p-bromophenyl)-ethanol of Example 2 in the same way as thechloro analog; methanol was used as the solvent for recrystallization. M.P. 42.0-42.8 C. Analysis m m 'a a) 1 Calculated Found Calculated Found EXAMPLE 6 Dehydrofluoridation pr0ducts-- (C H Hal) czCHF, 2- flu0r0-1,1-bis-(p-halophenyl)-ethene 3.8 grams of "2,2-difiuoro-1,l-bis-(p-bromophenyl) ethane '(Ex. 5) were dehydrofluorinated (removal of 1 mole of hydrogen fluoride) by heating under reflux for 2.5 hours with 60 ml. of 2% ethanolic potassium hydroxide. The solvent was removed under reduced pressure and the residue extracted with several portions of ether. The combined ethereal extract was washed with water and driecl'over magnesium sulfate. Removal of the ether afiorded a colorless oil which was distilled at diminished pressure. Upon recrystallization with methanol there was obtained an yield of 2-fiuoro-1,lbis-(p-bromophenyl)-ethene crystals having a M.P. of 84.2-85.2 C. Analysis (C H Br F):

Calculated Found Crystals of 2-fluoro-1,1-bisr(chlorophenyl)-ethene were obtained in the same manner from 2,2-difiuoro-1,1-bis- (p-chlorophenyD-ethe-ne of Example 5, in an 85% yield; M.P. 78.0-79.5? C. Analysis (C H Cl F):

Calculated Found it Z-ii uoro-l;hbis-(p-fluorophenyl) ethene was ob tained from 2,2-difluoro-1,l-bis-(p-fluorophenyl)-ethane in a 93% yield; Bl. 81-82 C.- at 1 mm.-pressure, index of refraction n 1.5481. Analysis (C H F parts .ofDDT was found to have an LD of 3.9, which is;

less potent than most of our new compounds.

It appears from the foregoing test results that the comcamulated Found pounds of the present invention are effective as insecticides, even when applied alone to insects which have not 0 7 ,7 7 yet bred immunity to DDT, even though the quantity of H our fluoro compounds to achieve the desired insect mor- -However, as pointed out, the principal utility of our compounds is in the field of DDT synergis-ts where, as shown in the foregoing table, a most surprising reduction of quantity of synergistic mixture (as compared with the quantity of DDT alone) results in effective kills of DDT-resistant insect strains (the efiectiveness of the compositions being in inverse ratio to their numerical LD ratings). This is borne out by a control computation on the synergistic effect on a number of the above 2,2di-v fluoro compounds, as compared with the synergistic effectwith DDT of the corresponding 2,2,2-trifluoro compounds test-4 replicates of flies each duplicated from 2 dif- 20 reported by Tahori, supra.

TABLE II 1 Part 2 2-Di 1 Part 2,2,2- 1 Part 2,2,2- Fluoro filom- Trifluoro Trttluoro pound to 5 Compound Compound Parts DDT to 1 Part to 10 Parts DDT DDT 2,2-Dlfiuoro-l,1-bis-(p-chlorophenyl)ethane---. 171 2,2,2-Trtfiuoro-1,l-bis-(p-chlorophenyl)ethane l4 0 2,2-Ditluor0-1,1-bis-(p-chlorophenyl)-ethanol 194 2,2,2-TrLfluoro-1,1-bls-)p-chlorophenyl)ethanol 15 2,2 Difl110i'0-1,l-bis-(p-chlorophenyl(-ethyl acetate- 71 2,2,2-Trlfiuoro-l,1-b1s-(p-chlorophenyl)ethyl acetate- 15 11 2,2-Difluor0-1,1-bis-(p-brornophenyl) -ethane 125 2, 2, 2-T rifiuoro -l,l-bis-(p-bromophenyl) ethane 10 0 2,2-Ditluoro-1,l-bls-(p-bromophenyl) -eth anol 169 2,2,2-TrLfluoro-l, l-bis-(p-brom ophenyl) ethanol 16 12 2,2-Difiuor0-L1-bis-(p -bromophenyl) ethyl acetate. 71 2,2,2-Trlfluoro -l,l-bls (pbromophenyl) ethyl acetate. 14 10 2,2-Dlfluoro-l,l-bis-(p-fluoroplienyl) ethanol 42 2,2,2-Trifluoro -1,1-bis-(p-fluoroph enyl) -ethan0l c 10 10 ferent-fly populations. The quantity of test compound required to kill 50% of'the test flies (LD-SO) was determined by plotting on a logarithmic scale percent mortality versus doses of test compound.

. The second column of test results shows the synergistic action of our compounds in combination with DDT, when applied to a DDT-resistant strain of adult female houseflies in the same manner. The ratio of fluoro compounds to DDT was one part of fluoro compound to 5 parts of DDT.

TABLE I reason of Tahoris comparison of that strain with a Berkeley strain, to have less immunity to DDT than LDEO the DDT-resistant houseflies on which our tests were conducted. DDT-Suscep- DDT-Reslstr time Flies, ant Flies 1 For economic reasons it is advisable to apply our new Fluom o Part F1110, insecticldes, when used as the sole active ingredient or in P $gg synergistic combination with DDT, by the use of a proper solid or liquid diluent, e.g., of the type customarily used 2,2 Dmuom 1,l bis p cmorophenyl) with DDT, such as carbon black, talc, pyrophyllite, hy-

ethane 2.2 0.96 drocarbon solvent, alcohol, or aqueous emulsion. g gggfifjlk fjflfi f ffi fi i g' 3 8 0 62 The term DDT, as used in the specification and claims, 2,2-Difluoro-l,1-bis-(p-chlorophenyl)- denotes dichlo-rodiphenyltrichloroethane (pure or tech 2 eit lliyl aeefalteg m h l) 9.4 1.6 nical grade) norolS p-c crop eny ethane 22 11.5 It will thus be seen that we have provided a series of 21 0.96 new insecticidal compounds which are particularly effec 2,2-lgifluinrodd-bis-(p-bromophenyl)- tive as DDT synergists; they may be arranged as to the F figg fj ziib' gjf:fiimagfiiyfif degree of synergistic efficiency in the following general ethyl acetate. 9. 7 1. 7 order: 2-ltllluoro-Ll-bis bromophenyl)- 20 7 2 2 difl 1 1 b h 1 h l) h .1 e ene .1 uoro- 1spaop eny -et anos 'ii riifi ffifiif i. fffff fii l- 5.1 1.0 i i -(pp y m ggg ro-L -(p-fi p y 7 2 2 s 2,2-difluoro-l,1-b1s-(p-halophenyl)-ethyl acetates ,555: gggqg mg 55 31 2-fluoro-1,1-b1s.(p-ha1ophenyl)-ethenes ethyl acetate 35 8.5 2-F1l1uoro-Ll-bis-(p-fiuorophenyl)- 18 28 Bromine and chlorine are generally superior to fluorine .t-et ene; Control: DDT alone M5 as synergistically efiicient substltuents in the phenyl groups of the above-named compounds; while the para 1 (N o fluoro compound, 6 parts DDT.)

In a further control experiment with the DDT-resistant strain of flies. a mixture of 1 part of 1,1-bis-(p-chlorophenyl)-ethanol (DMC, a known DDT synergist) and 5 position is generally preferred, the meta and ortho posi-' tions are not excluded from the purview of our invention.

Having thus described our invention and several modes by which the same may be carried into practice, it will be clear that several modifications and changes thereof may be madc without departing from the spirit of our invention or from the scope of the subjoined claims. We thus desire to claim our invention as broadly as the prior art Hal wherein Hal and Hal are halogen atoms having an atomic weight not above 80 and wherein Y is a member of the group consisting of hydrogen, hydroxyl and acetoxyl, and of a compound having the formula:

Hal

Hal

wherein Hal and Hal have the same meanings as aforesaid, said synergist being present in an amount not in excess of the amount of said DDT.

2. An insecticidal composition comprising as its essential active ingredients DDT and as a synergist therefor a 2,2-difluoro-l,l-bis-(p-halophenyl)ethane, the atomic Weight of the halogen atom attached to phenyl being not above 80, said synergist being present in an amount not in excess of the amount of said DDT.

3. An insecticidal composition comprising as its essential active ingredients DDT and as a synergist therefor a 2,2-difluoro-1,1-bis-(p-halophenyl)-ethanol, the atomic weight of the halogen atom attached to phenyl being not above 80, said synergist being present in an amount not in excess of the amount of said DDT.

4. An insecticidal composition comprising as its essential active ingredients DDT and as a synergist therefor a 2,2 difluoro 1,1-bis-(p-halophen yl)-ethyl acetate, the atomic weight of the halogen atom attached to phenyl being not above 80, said synergist being present in an amount not in excess of the amount of said DDT.

5. An insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,1-bis-(pchlorophenyD-ethane as a synergist therefor, said synergist being present in an amount not in excess of the amount of said DDT.

6. An insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,1-bis-(pchlorophenyl)-ethanol as a synergist therefor, said synergist being present in an amount not in excess of the amount of said DDT.

7. An insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,l-bis-(pchlorophenyl)-ethyl acetate as a synergist therefor, said synergist being present in an amount not in excess of the amount of said DDT.

8. An insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,l-bis-(pbromophenyl)-ethanol as a synergist therefor, said synergist being present in an amount not in excess of the amount of said DDT.

9. An insecticidal composition comprising as its essential active ingredients DDT and as a synergist therefor a Z-fluoro-l,l-bis-(p-halophenyl)-ethene, the atomic weight ofthe halogen atom attached to phenyl being not above 80, said synergist being present in an amount not in excess of the amount of said DDT.

10. An insecticidal composition comprising as itsessential active ingredients DDT and 2-fluoro-l,1-bis- (p-bromophenyl)-ethene as a synergist therefor, said synergist be- 8 ing present in an amountnot in excess of the-amount of said DDT. f t

' 11. Method of killing DDT-resistant insects which com-- prises'contacting them with a synergistic insecticidal composition comprising' as its essential active ingredients- DDT and a member of the group consisting of a corn pound having the formula:

I o I Y Hal a1 wherein Hal and Hal are halogen atoms having an atomic weight not above 80 and wherein Y is a member of the group consisting of hydrogen, hydroxyl and acetoxyl, and of a compound having the formula:

Hon Q Q Hal a1 wherein Hal and Hal have the same meanings as aforesaid. a

12. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and a 2,2-difluoro-1,l-bis-(p-halophenyl)ethane, the atomic weight of the halogen attached to phenyl being not above 80.

- prises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,1bis(p-chlorophenyl)-ethane.

16. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro- 1,1-bis-(p-chlorophenyl)-ethanol.

17. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-l,l-bis-(p-chlorophenyl)-ethyl ace:

tate.

18. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and 2,2-difluoro-1,1'bis-(p-bromophenyl)-ethanol.

19. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and a Z-fluoro-1,1-bis-(p-halophenyl)-ethene, the atomic Weight of the halogen attached to phenyl being not above 80.

20. Method of killing DDT-resistant insects which comprises contacting them with a synergistic insecticidal composition comprising as its essential active ingredients DDT and Z-fiuoro-l,l bis-(p-bromophenyl)-ethene.

21. Method of killing insects which comprises contact ing them with a Z-fluoro-1,1-bis-halophenyl-ethene, the atomic weight of the halogen atom attached to phenyl being not above 80.

' (References on following page) References Cited in the file of this patent Re. 22,700 Re. 22,922 2,238,242 2,455,643

UNITED STATES PATENTS 10 OTHER REFERENCES Jour. Econ. Ent., vol. 41, June 1948, pp. 416-421 er Dec. 4, 1945 (Table N0. 2, p. 418 relied on); v01. 48 (1955), pp. M ller Sept. 30, 1947 5 638442. Balon Apr. 15, 1941 J.A.C.S., vol. 77 (1955), pp. 4164-4168.

Bakalar Dec. 7, 1948 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION 1 Patent No .2,990,32l June 27 1961 Joseph Bornstein et a1.

It is hereby certified that error appears in ,the above numbered patentrequiring correction and that the said Letters Patent should read as "corrected below.

Column 4, line 65 for "-ethene" read -=ethane 7 same column 4, in,,.the fifth table thereof, column 2 line 3 thereof for "26.52" read 26.53 column 5 line 38 for "doses" read dose columns 5 and 6, TABLE II, column 3 line 2 thereof for ")pchlorophenyl) read -=(p=chlorophenyl) same TABLE II, column 1, line 3 thereof for "=-(p-=ch1orophenyM read (pchlorophenyl) Si ned and sealed this 23rd day of January 1962.

(SEAL) Attest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents 

11. METHOD OF KILLING DDT-RESISTANT INSECTS WHICH COMPRISES CONTACTING THEM WITH A SYNERGISTIC INSECTICIDAL COMPOSITION COMPRISING AS ITS ESSENTIAL ACTIVE INGREDIENTS DDT AND A MEMBER OF THE GROUP CONSISTING OF A COMPOUND HAVING THE FORMULA: 